Serum paraoxonase and its influence on paraoxon and chlorpyrifos-oxon toxicity in rats.
Costa-LG; McDonald-BE; Murphy-SD; Omenn-GS; Richter-RJ; Motulsky-AG; Furlong-CE
Toxicol Appl Pharmacol 1990 Mar; 103(1):66-76
Serum paraoxonase activity and its influence on paraoxon (311455) and chlorpyrifos-oxon (5598152) (CPO) toxicity were studied in rats and rabbits. Blood samples were obtained from male Sprague-Dawley- rats and New-Zealand-white-rabbits and assayed for serum paraoxonase activity. Rats and rabbits were then injected intraperitoneally (ip) with paraoxon to determine the minimum dose (MED) causing cholinergic symptoms. Paraoxonase activity in rabbit serum was significantly higher than in rat serum, 1005 versus 140 units (U) per liter. The MEDs for causing signs of cholinergic intoxication were 0.5mg/kg in rats and 2.0mg/kg in rabbits. Rats and rabbits were injected ip with the paraoxon MEDs. They were killed 1 hour later and the diaphragm, plasma, hippocampus, and cortex were taken and assayed for cholinesterase (ChE). ChE activity was inhibited to about the same extent, 21 to 60%, in the tissues of both species. Rats were injected intravenously (iv) with 8.5U purified paraoxonase from rabbit serum. Blood samples were obtained at various times up to 24 hours later and assayed for paraoxonase. Other rats were injected with rabbit serum paraoxonase as before. Thirty minutes later they were given 0.1 to 2mg/kg paraoxon iv, ip, orally, or dermally. They were killed 4 hours later and ChE activity in the plasma, erythrocytes, brain, and diaphragm was determined as an index of paraoxon toxicity. A similar experiment was performed with immediate eight to ten fold increases in rat serum paraoxonase activity. Paraoxonase activity slowly decreased thereafter, but was still significantly elevated after 24 hours. Enhanced serum paraoxonase activity protected rats against paraoxon toxicity when it was given iv. Partial protection was afforded when it was given ip or dermally. Enhanced serum paraoxonase activity also protected against CPO toxicity particularly when it was given iv or dermally. The authors conclude that increasing serum paraoxonase activity in rats decreases their sensitivity to paraoxon and CPO.
NIOSH-Publication; NIOSH-Grant; Blood-serum; In-vivo-studies; Laboratory-animals; Genetic-factors; Enzyme-activity; Cholinesterase-inhibitors; Organo-phosphorus-compounds; Dose-response; Biochemical-indicators
Environmental Health University of Washington Dept of Environ Hlth, SC-34 Seattle, WA 98195
Toxicology and Applied Pharmacology
University of Washington, Seattle, Washington